Outcome Measures: |
Primary: Part A - Myocardial glucose uptake, Difference in myocardial glucose uptake between 0.9% saline, glucagon:exenatide and glucagon scan as measured by 18F-FDG, Comparison between scans over a maximum period of 16 weeks|Part A - Global longitudinal strain / global circumferential strain / global radial strain, Difference in global longitudinal strain / global circumferential strain / global radial strain between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR, Comparison between scans over a maximum period of 16 weeks|Part A - Ejection fraction, Difference in ejection fraction between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR, Comparison between scans over a maximum period of 16 weeks|Part A - Stroke volume, Difference in stroke volume between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR, Comparison between scans over a maximum period of 16 weeks|Part A - Cardiac output, Difference in cardiac output between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR, Comparison between scans over a maximum period of 16 weeks|Part B - Changes in phosphocreatine/adenosine (PCr/ATP) radio, Changes in PCr/ATP radio between 0.9% saline, glucagon:exenatide and glucagon (optional) in the mid-interventricular septum as a measure of cardiac energy status as measured by 7T phosphorus (P) 31 magnetic resonance spectroscopy (MRS), Comparison between scans over a maximum period of 16 weeks|Part B - Changes in absolute concentrations of PCr and ATP defined by AHA 17- segment territory as a measure of cardiac energy status (determined by 31P-MRS), Changes in absolute concentrations of PCr and ATP between 0.9% saline, glucagon:exenatide and glucagon (optional) as defined by AHA 17-segment territory as a measure of cardiac energy status (determined by 7T 31P-MRS), Comparison between scans over a maximum period of 16 weeks | Secondary: Part A - End systolic/diastolic ventricular/atrial volumes, Difference in end systolic/diastolic ventricular/atrial volumes between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR, Comparison between scans over a maximum period of 16 weeks|Part A - Radial strain, Difference in radial strain between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR, Comparison between scans over a maximum period of 16 weeks|Part A - Global systolic/diastolic longitudinal/circumferential/radial strain rate, Difference in global systolic/diastolic longitudinal/circumferential/radial strain rate between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR, Comparison between scans over a maximum period of 16 weeks|Part A - Relationship between early and late filling (from mitral flow), Difference in early and late filling (from mitral flow) between 0.9% saline, glucagon:exenatide and glucagon scan as measured by CMR, Comparison between scans over a maximum period of 16 weeks|Part A/B - Heart rate, Difference in heart rate between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks|Part A/B - Blood pressure, Difference in blood pressure between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks|Part A/B - Glucose, Difference in glucose between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks|Part A/B - Glucagon, Difference in glucagon between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks|Part A/B - Insulin, Difference in insulin between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks|Part A/B - C-peptide, Difference in C-peptide between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks|Part A/B - fatty acids, Difference in fatty acids between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks|Part A/B - exenatide, Difference in exenatide between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks|Part A/B - Total GLP-1 and total active GLP-1, Difference in GLP-1 between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks|Part A/B - gastric inhibitory polypeptide, Difference in gastric inhibitory polypeptide between 0.9% saline, glucagon:exenatide and glucagon, Comparison between infusions (placebo vs drug) over a maximum period of 16 weeks
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